Project Summary/Abstract Osteoporosis is a progressive bone disease that reduces bone mineral density (BMD) leading to an increased risk of bone fracture. It largely affects women post-menopause who incur a sharp decline in estrogen production, which has a key role in the proper growth and maturation of bone. Alternative and integrative health approaches for preventing disease occurrence, primarily through use of natural dietary supplements, are currently being sought due to the adverse health risks associated with conventional hormone replacement therapies. To assess the effectiveness of these disease interventions, a well-established novel and sensitive screening technique incorporating a biological tracer, calcium-41 (41Ca), is used to rapidly and sensitively monitor bone resorption. Measured is the urinary 41Ca:Ca isotope ratio, monitored by Accelerator Mass Spectrometry (AMS) to detect changes in bone calcium metabolism. This study proposes to develop a 41Ca simulation study to serve as a tool to investigate how inputs of sample size, number of control periods, and number of control samples per period will affect the output: (1) the accuracy (standard error) of reported mean estimates of treatment effect (2) the power of the study to detect given effect sizes and (3) the cost of the experimental study. Ultimately, this tool will determine ?optimal? 41Ca experimental designs, which are uniquely defined as the most efficient study designs that preserve the accuracy and reliability of the original experimental estimates but require a reduced number of experimental samples, which notably provides a cost reduction. In parallel, this study proposes to develop a 45Ca simulation tool using the ovariectomized (OVX) rat model to determine the optimal experimental design for treatment efficacy on bone calcium retention. Ultimately, these new designs will be implemented to further increase the practicality and utility of 41Ca and 45Ca methodology in future translational research studies, targeted to reduce the risk of osteoporosis. This proposal specifically addresses the 2016 NCCIH strategic plan Objective 1: Advance Fundamental Science and Method Development, by creating a novel research study tool for strengthening (statistical power) the experimental design of human and animal trials of alternative and complementary health approaches. In addition, this proposal will provide the necessary research training skills and mentorship opportunities for effective scientific communication through grant and proposal writing, oral presentations, and participation in collaborative research environments and science diversity mentorship programs. I anticipate that by acquiring these skills and opportunities, I will be successful in a professional career as independent research scientist.